Expression patterns of promoters for Npy Y1 and Y5 receptors in Y5ritta and Y1rvenus bac transgenic mice

In the rat brain Y1 and Y5 receptors are co-expressed in various forebrain regions where they mediate several NPY-activated functions, including feeding behaviour, anxiety, neuronal excitability and hormone secretion. We studied the distribution pattern and cellular colocalization of the Y1 and the Y5 receptor gene expression in the mouse brain by using transgenic mice with genomically integrated BAC clones, where the coding regions of the Y1 and Y5 receptor genes were replaced by Venus and the synthetic transcription factor itTA reporter genes, respectively (TgY5RitTA/Y1RVenus mice). Analysis of Venus fluorescence and itTA-mediated activation of Cre recombinase revealed copy number-dependent expression levels, between the lines, but similar expression patterns. In three transgenic lines the BAC encoded Y5 receptor promoter induced strong Cre expression in the olfactory system, cerebral cortex, hippocampus and basal ganglia. Weaker expression was found in most of the hypothalamic nuclei of line 25, the highest-expressing transgenic line. Activation of Cre was itTA-dependent and could be regulated by doxycycline. The Y1 receptor promoter-induced Venus fluorescence was intense, widely present through the brain and colocalized with Cre immunostaining in neurons of distinct brain regions, including the cerebral cortex, basolateral amygdala, dentate gyrus and paraventricular nucleus. These data provide a detailed and comparative mapping of Y1 and Y5 receptor promoter activity within cells of the mouse brain. The TgY5RitTA/Y1RVenus-transgenic mice generated here also represent a genetic tool for conditional mutagenesis via the Cre lox system, particularly of genes involved in feeding behaviour, neuronal excitability and hormone secretion.